DESCRIPTION: The central focus of this research will be the use of affinity capillary electrophoresis (ACE), in combination with charge ladders derived from proteins, to investigate electrostatic interactions important in protein biochemistry: acidities of functional groups, interactions among charged groups on proteins, electrostatic contributions to binding of ligands to proteins, and screening of electrostatic interactions involving proteins by ions in solution. These studies will be extended by detailed experimental studies of small, non-protein biomolecules (vancomycin and its derivatives, cyclodextrins and their derivatives, substrates such as ATP, cofactors such as NAD(P)(H), oligonucleotides), and by theoretical analyses based on the Poisson-Boltzmann equation. The research will also apply ACE to problems in biomolecular recognition that do not explicitly involve electrostatic interactions: polyvalency will be the most important of these problems.